Originally considered to be a milder version of bipolar disorder (BD), research now indicates bipolar disorder- not otherwise specified (BP-NOS) is a highly impairing condition. Considerable gains have been made recently in understanding BP-NOS, in large part by research utilizing clear operational definitions for BP-NOS (cf. the NIMH-funded Course and Outcome of Bipolar Youth [COBY] and Longitudinal Assessment of Manic Symptoms [LAMS] studies). However, clinical trials have focused on youth with Bipolar Disorder- Type I (BP1). No clinical guidelines exist for the treatment of BP-NOS. BP-NOS is similar to BP1 and BP2 in terms of peak symptom severity, suicidal ideation, and number of comorbidities;it is similar to BP2 in terms of functional impairment (Axelson et al, 2006). However, youth with BP-NOS are three times slower to recover and experience more mood lability than youth with BP1 or BP2 (Birmaher et al, 2006). They are also more likely to remain sub- syndromal rather than becoming asymptomatic compared to youth diagnosed with BP1 and BP2 (Birmaher et al, 2006). Available evidence-based pharmacotherapy guidelines are for BP1;efficacious medications are, unfortunately, associated with significant risk for adverse events (Kowatch, Fristad, Findling &Post, 2009). Thus, there is a greater imbalance in the risk:benefit ratio of treating these youth with psychotropics compared to the risk:benefit ratio of treating youth diagnosed with BP1, for whom we have clinical trial data. Previous research on diet and nutrition suggests that omega-3 (?3) fatty acids have a beneficial effect on mood, which might provide either a primary or adjunctive treatment with a more favorable risk:benefit ratio for children suffering from BP-NOS than currently available pharmacologic interventions. Psychoeducational psychotherapy (PEP) also has shown promise in treating bipolar spectrum disorders in children aged 8-12 (Fristad, 2006;Fristad, Verducci, Walters, &Young, 2009);its efficacy in treating BP-NOS specifically has not been determined. The current study compares ?3, PEP, and their combination to a placebo supplement and active monitoring (AM) in a 12-week trial of 60 children with BP-NOS (15 each with ?3, ?3 plus PEP, PEP, and placebo, all with active monitoring). Primary goals are to determine: 1) feasibility of a) recruiting 60 participants in 2 years;b) participant retention over a 12-week trial;and 2) placebo-controlled effect sizes for ?3, PEP, and combination treatment on manic and depressive symptoms. Secondary goals are to explore response curves over time, mediators and moderators, treatment response across a broad array of outcome variables, adherence to treatment, impact on physiologic parameters often worsened by mood stabilizing medications, and experience of side- effects in participants receiving ?3 and/or PEP. Comparisons of results to a parallel study of children with depression with identical design will maximize knowledge gained. This pilot study of ?3, PEP, and combined treatment will provide evidence about whether a larger trial is feasible and justified. PUBLIC HEALTH RELEVANCE: Childhood onset bipolar disorder-not otherwise specified (BP-NOS) is highly impairing. However, no treatment guidelines are designed specifically for it;current clinical practice is guided by treatments for BP1. Limitations of currently available treatments have led researchers to explore alternatives for more effective and/or safer treatment options;long-chain omega-3 fatty acids and family-based psychoeducational psychotherapy (PEP) have promising but non-decisive preliminary results. This small randomized, controlled study will examine feasibility of studying the effects of ?3 dietary supplementation, PEP, and combined treatment on reducing symptoms of depression and mania in children diagnosed with BP-NOS. Knowledge will be maximized by comparing results to those from a parallel study for children with depression.